This work explores the functional aspects of F- binding by protein(s) of newly deposited enamel matrix. The findings are summarized as follows. Flow rate dialysis was used to measure the fluoride-binding characteristics of the organic matrix from fetal bovine enamel. The matrix from newly deposited enamel had 5.78 times 10 to the minus 5th power moles/g of high affinity binding sites for fluoride with a dissociation constant of 1.1 times 10 to the minus 6th power M. The matrix from enamel in the late stages of mineralization had 4.36 times 10 to the minus 5th power moles/g matrix of binding sites with a dissociation constant of 3.2 times 10 to the minus 6th power M. In the physiologic range of fluoride concentrations, fluoride bound by the early matrix could account for up to forty times the fluoride bound per unit weight of enamel by the late matrix. It is proposed that early enamel matrix buffers the newly deposited enamel against transitory fluctuations in local fluoride concentrations. Other phases of the study, in progress at this time, are concerned with in vitro and in vivo effects of F- on early enamel formation as related to the F- binding mechanism.